SMAD2, SMAD3 and TGF-β GENE expressions in women suffering from urge urinary incontinence and pelvic organ prolapse.

We evaluated the changes in the levels of TGF-β and SMAD gene and protein expression in the uterosacral ligament (USL) of patients with concomitant pelvic organ prolapse (POP) and urgency urinary incontinence (UUI) to illuminate the pathophysiology of UUI. The TGF-β pathway is involved in collagen synthesis and degradation. The Transforming Growth Family-β (TGF-β) superfamily has essential intracellular signaling components, such as newly identified SMAD family members. We evaluated the changes in the levels of TGF-β and SMAD gene and protein expression in the USL of patients with concomitant pelvic organ prolapse (POP) and UUI. This study included 10 patients who had been diagnosed with POP and UUI in the study group and 14 asymptomatic women without complaints of POP and UUI in the control group. Biopsy samples were collected from bilateral USL tissues during vaginal or abdominal hysterectomy. Total RNA was extracted from USL tissue and analyzed by qPCR. The protein expression levels were also analyzed with ELISA. In UUI patients, SMAD3 and TGF-ß1 gene expression levels significantly decreased compared to the control patients (p = 0.008 and p = 0.006, respectively). SMAD2 mRNA levels did not differ between the study and control groups (p = 0.139). No differences was found in the levels of SMAD2, SMAD3, and TGF-ß1 protein expression between the two groups. The reduction in the gene and protein expression levels of SMAD3 and TGF-ß1 in women with UUI and lax uterosacral ligaments may indicate a causal link.Clinical trial registration: NCT04525105.